optically monitoring the progress of DNA
sequencing. “We knew the fundamental
limitation in fluorescence-based sequencing would be background noise caused by
other nucleotides,” says Stephen W. Turner,
founder and chief technology officer of Pacific Biosciences, who was on the team that
invented the zero-mode waveguides. “We
needed to reduce the observation volume.”
Turner and his Cornell colleagues tried
several approaches. “Most of them worked
to some degree, but the zero-mode waveguide worked so well and was so much
better and simpler than the others that it
was the hands-down winner,” Turner says.
The technology is now the heart of Pacific Biosciences’ PacBio RS II sequencing
instrument.
Each waveguide in a
These reaction
disposable PacBio RS II
cells for the
PacBio RS II
reaction cell serves as a
tiny vessel for a DNA-se- DNA sequencer
150,000
quencing reaction. Single contain
zero-mode
polymerase enzymes are waveguides
immobilized in a wave(holes not
guide, which provides
visible).
the University of Washington. “That, along
with the long read lengths, is enabling its
utility in niche applications such as accurate assembly of microbial genomes with
high or low GC content, as well as accurate
assembly of challenging regions of mammalian genomes.”—CELIA ARNAUD
MATERIALS CHEMISTRY:
METAL-ORGANIC
FRAMEWORKS GO
COMMERCIAL
Record-breaking surface areas, exceptional
pore sizes, and cavernous internal channels
are properties that thrust metal-organic
framework (MOF) materials into the
scientific spotlight just over a decade ago.
Researchers quickly predicted that these
porous crystals—built from metal ions or
metal clusters bridged by organic linking
groups—would prove useful for gas separation and storage and other applications.
Then in 2003, a team led by Omar M.
Yaghi, now at the University of California,
PACIFIC BIOSCIEN CES
surfaces, which can be used as enantioselective catalysts or for sensing chiral
molecules (Nature 2003, DOI: 10.1038/
nature01990). The two images, created in
the lab of Jay A. Switzer at Missouri University of Science & Technology, are graphical
representations of X-ray diffraction data.
The peaks are stereographic projections—
so-called pole figures—showing the crystal
orientation of enantiomeric copper oxide
films electrodeposited on achiral gold substrates. Switzer’s team used right- or lefthanded tartrate molecules in the deposition
solution as templates to orient the films
with right- or left-handed chirality.
Since 2003, Switzer’s group has deposited
chiral copper oxide on different substrates
and shown that the enantiospecificity can
be enhanced by etching the films using chiral etchants (J. Am. Chem. Soc. 2007, DOI:
10.1021/ja073640b). “I am sad to announce
that I have not formed a start-up company
and made billions of dollars—yet,” Switzer
informs C&EN. Switzer’s lab is still working on electrodeposition of metal oxide and
metal hydroxide films, with an eye toward
developing oxygen-evolving catalysts for
splitting water to produce hydrogen (Chem.
Mater. 2013, DOI: 10.1021/cm400579k) and
to make switches for solid-state memory
devices being designed for smartphones
and tablet computers (ACS Nano 2013, DOI:
10.1021/nn4038207).—STEVE RITTER
DNA SEQUENCING:
ZERO-MODE
WAVEGUIDES TURN 10
A decade ago, researchers at Cornell University reported an analytical device, which
they called a zero-mode waveguide, for
using light to detect single biomolecules in
samples of any concentration. That device
was remarkably simple—just an array of
nanometer-scale holes in a metal film on
a fused-silica surface (Science 2003, DOI:
10.1126/science.1079700). Today, that
unpretentious device is the basis of the
DNA-sequencing technology from Pacific
Biosciences, based in Menlo Park, Calif.
Waveguides are devices that are used
to direct light and sound waves—optical
fibers are one example. Zero-mode waveguides are so named because the holes,
which serve as the waveguides, are smaller
than the wavelength of light used, so the
light doesn’t pass through the holes.
From the beginning, the Cornell team’s
waveguides were intended to be used for
a window to observe sequencing in real
time by precisely following the incorporation of fluorescently labeled nucleotides.
The prototype device had a few thousand
waveguides, but today’s PacBio RS II uses
reaction vessels with 150,000 waveguides
that can be monitored simultaneously.
The combination of the waveguide and
specially designed DNA polymerases allows
sequence read lengths that are thousands of
base pairs long—some longer than 30,000
base pairs, which is the most among DNA
sequencers.
Other sequencing devices sometimes
have trouble working through DNA regions
containing a lot of guanine and cytosine
(GC) bases, but not the PacBio RS II. “The
place where PacBio is truly amazing is its
lack of GC bias,” comments Jay Shendure,
associate professor of genome sciences at
CEN.ACS.ORG
34
DECEMBER 23, 2013
Berkeley, reported that a zinc-based
MOF could reversibly store a few percent
by weight of hydrogen at room temperature and more at lower temperatures (Science 2003, DOI: 10.1126/science.1083440).
That development was considered a step
toward the practical use of hydrogen as a
fuel for electric cars, and it sparked a flurry
of activity by scientists working on hydrogen storage, which continues today. A hydrogen uptake as high as 10% by weight has
been reported for a copper-based MOF at
high pressure and cryogenic temperature.
Researchers today have synthesized
thousands of MOFs and related types of
framework compounds and demonstrated
that many of them are useful for storing
and purifying gases, separating hydrocarbons, capturing carbon dioxide from
BASF (BOTH)
exhaust gas streams, mediating catalytic
reactions, and soaking up uranium from
seawater. Most of the reports—especially
ones detailing the structures and compositions of new MOFs—come from academic
research groups. But MOFs are no longer
just academic curiosities. A few companies,
including Sigma-Aldrich, now sell lab quantities of MOFs. And BASF makes a handful
of the compounds on a ton scale, although
commercial applications for them remain
scarce.
“We manufacture
double-digit-ton quantities of some MOFs
per production run,”
says BASF Senior Vice
President Ulrich Müller. He adds that the
company’s manufacturing capabilities have
already been optimized, so no additional
development work is needed; the company
is just waiting for demand to pick up.
One application for BASF’s MOFs is to
boost the storage capacity of natural gas
fuel tanks for vehicles such as buses. The
BASF now manufactures a few
types of MOFs on a multiton
scale at its facilities in Germany
(above). The porous crystals are
starting to be used in commercial
applications, including sorbent
materials that increase the gas
storage capacity and driving
range of natural-gas-burning
vehicles, such as this truck (left).
extreme surface area of a MOF—thousands of square meters per gram—and
its ability to adsorb methane and other
natural gas molecules mean that cylinders
packed with MOFs can store roughly twice
as much natural gas as unfilled cylinders.
Speed Matters
Speed matters when it comes to disseminating your high quality
research. With a growing portfolio of Letters journals, leading their
respective felds and offering submission to web publication in as little as
4 weeks, the ACS recognizes the importance of helping researchers win
the race to communicate vital discoveries.
This speed is achieved without compromising the ACS standards of
rigorous peer review, while providing the added value of expert technical
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CEN.ACS.ORG
35
DECEMBER 23, 2013
The technology has been road tested on
passenger vehicles and large trucks.
Müller has been closely following MOF
developments coming out of academic labs
since the end of the 1990s. Yet these materials continue to amaze him.
“It’s fascinating to see the way tuning and
tweaking the metals and linkers can lead to
new materials with properties that would
have been unimaginable just a few years
ago,” Müller says. Translating some of these
newer materials into real-world applications seems inevitable, he adds. But as with
any new technology, Müller concedes, commercialization takes time.—MITCH JACOBY